AEGiS-15IAC: Self-emulsifying drug delivery systems (SEDDS) for ritonavir oral solution.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Self-emulsifying drug delivery systems (SEDDS) for ritonavir oral solution.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10030)

Arunothayanun P, Pirayavaraporn C, Watnasirichaikul S, Eksaengsri A
Research and Development Institute, Government Pharmaceutical Organization, Bangkok, Thailand

BACKGROUND: To develop a clear ritonavir oral solution which can self-emulsify on diluting with water. The effects of each constituent contained in a self-emulsifying drug delivery system were studied.

METHODS: The self-emulsifying drug delivery systems (SEDDS) were developed for preparing of a clear ritonavir oral solution. The effects of solvents and co-solvents including alcohol, water, propylene glycol, polyethylene glycol 300 (PEG 300) or polyethylene glycol 400 (PEG 400), and a surfactant, being polyoxyl 35 castor oil (P35, HLB of 12-14) or polyoxyl hydrogenated 40 castor oil (PH40, HLB of 14-16), were investigated. The obtained clear ritonavir solutions were observed for self-emulsification on diluting with water.

RESULTS: In the SEDDS with equal alcohol content (43% v/v), PH40 allowed wider variation of water and propylene glycol content when comparing with those using P35 as a surfactant. With 10.5% w/v PH40, as a surfactant, a wider range of water content (11.8-23.8 %v/v) can be added to obtain clear ritonavir solutions (8g ritonavir in acidic medium) while P35 allowed a narrow range of water content (18.8-21.8 %v/v). At low alcohol content (35 %v/v), polyethylene glycol (PEG 300 or PEG 400) was found to improve the solubility and reduce the recrystallization of ritonavir. Microscopic observation revealed that clear solutions of ritonavir SEDDS formulated with alcohol varied from 35-45 %v/v, water 12 %v/v, propylene glycol, PEG 400, and PH40 formed emulsion spontaneously on dispersing in water.

CONCLUSIONS: A clear ritonavir oral solution was successfully developed with low alcohol content by using polyoxyl hydrogenated 40 castor oil as a surfactant and PEG400 as a co-solvent. Formation of an emulsion on dispersing the ritonavir SEDDS in water can prevent drug precipitation and may improve drug absorption.

Keywords: AEGIS, Drug Delivery Systems, Solubility, Polyethylene Glycols, Surface-Active Agents, Pharmaceutical Preparations, Solvents, Water, Propylene Glycol, Castor Oil, Propylene Glycols

040711
A10030